Drug-Drug Interaction Study of Vesatolimod in Adults With HIV-1 Who Have Very Low or Undetectable Virus Levels

Phase 1TerminatedNCT05458102

Gilead Sciences18 enrolled

Overview

The goal of this clinical study is to learn more about the impact of cobicistat (COBI) (P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), and strong cytochrome P450 enzyme \[CYP\]3A inhibitor), voriconazole (VOR) (strong CYP3A inhibitor), and rifabutin (RFB) (moderate CYP3A inducer) on the study drug, vesatolimod (VES), in people with HIV-1 on antiretroviral therapy (ART).

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Human Immunodeficiency Virus Type 1 (HIV-1) Infection

Interventions

VesatolimodDRUG

Administered orally

CobicistatDRUG

Administered orally

VoriconazoleDRUG

Administered orally

Rifabutin

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Key Inclusion Criteria: * On an antiretroviral therapy (ART) regimen for at least 6 consecutive months, with no change in the ART regimen within 2 months prior to screening. Permitted ARTs are as follows: * Cohort 1: A regimen of (bictegravir \[BIC\], dolutegravir \[DTG\], raltegravir \[RAL\], or doravirine \[DOR\]) plus Nucleoside Reverse Transcriptase Inhibitors (NRTIs). Examples of acceptable regimens include BIC/emtricitabine/tenofovir, DTG/ abacavir (ABC)/3TC, DTG/3TC, DTG + emtricitabine/tenofovir, or DOR/3TC/tenofovir * Cohort 2: A DTG-based regimen is required (DTG/ABC/3TC), (DTG/3TC), or (DTG + NRTIs) * Plasma HIV-1 RNA levels less than 50 copies/mL at screening * Have normal hematologic function with an absolute neutrophil count greater than or equal to 1.5 × 10\^9/L, platelets greater than or equal to 150 × 10\^9/L; hemoglobin greater than or equal to 10.5 g/dL for females and greater than or equal to 11.5 g/dL for males * Clusters of differentiation (CD) 4 T cell count greater than or equal to 350 cells/μL * Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less than or equal to 2.5 x upper limit of normal (ULN) and total bilirubin less than or equal to 1.5 mg/dL, or normal direct bilirubin and creatinine less than or equal to 1.25 x ULN * Have a calculated creatinine clearance (CLcr) of at least 60 mL/min (using the Cockcroft-Gault method) based on serum creatinine and actual body weight as measured at screening and upon admission * Individuals assigned female at birth and of childbearing potential who engage in heterosexual intercourse must agree to use protocol-specified method(s) of contraception * Must be willing and able to comply with all study requirements and available to complete the study schedule of assessments * In the judgment of the investigator, be in good general health, based on review of the results from a screening visit Key Exclusion Criteria: * Have received any study drug within 30 days prior to study dosing * Participation in any other clinical study (including observation studies) without prior approval from the sponsor is prohibited while participating in this study * Have current alcohol or substance abuse judged by the investigator to potentially interfere with individual compliance or individual safety, or a positive drug or alcohol test at screening or baseline * No Evidence of chronic hepatitis B virus (HBV) infection (defined as positive hepatitis B surface antigen \[HBsAg\] and/or positive HBV core antibody with positive reflex HBV DNA polymerase chain reaction (PCR)). Note: positive HBV core antibody with negative reflex HBV DNA PCR results are acceptable * No Evidence of active hepatitis C virus (HCV) infection (defined as positive hepatitis C antibody and HCV RNA above lower limit of quantitation). Note: positive anti-HCV antibody and negative HCV PCR results are acceptable * Acute febrile illness within 35 days prior to Day 1 * Have been treated with systemic steroids, immunosuppressant therapies, or chemotherapeutic agents within 3 months prior to screening or is expected to receive these agents during the study * Received any vaccine or immunomodulatory medication within 4 weeks prior to screening. Elective vaccination (eg, flu shot, hepatitis A or B vaccine) during the course of the study will require prior approval from the sponsor * Coronavirus disease of 2019 (COVID-19) vaccinations are allowed, with the requirement that they should not be administered within 7 ± 2 days of receiving VES * Have a history of any of the following: * Significant serious skin disease, such as but not limited to rash, food allergy, eczema, psoriasis, or urticaria * Significant drug sensitivity or drug allergy (such as anaphylaxis or hepatoxicity) * Known hypersensitivity to the study drugs, their metabolites, or to formulation excipients * Autoimmune disease * Significant cardiac disease or a family history of long QT syndrome, or unexplained death in an otherwise healthy individual between the ages of 1 and 30 years * Syncope, palpitations, or unexplained dizziness * Implanted defibrillator or pacemaker * Liver disease, including Gilbert syndrome * Severe peptic ulcer disease requiring prolonged (≥ 6 months) medical treatment * Medical or surgical treatment that permanently altered gastric absorption (eg, gastric or intestinal surgery). A history of cholecystectomy is not exclusionary * Have any serious or active medical or psychiatric illness (including depression) that, in the opinion of the investigator, would interfere with individual treatment, assessment, or compliance with the protocol * For Cohort 1, individuals with CYP2C19 genotype of CYP2C19\*2/\*2, CYP2C19\*2/\*3, or CYP2C19\*3/\*3 Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Locations (5)

Collaborative Neuroscience Research, LLC.

Long Beach, California, United States

Clinical Pharmacology of Miami, LLC.

Miami, Florida, United States

Advanced Pharma, CR, LLC.

Miami, Florida, United States

Triple O Research Institute, P.A.

West Palm Beach, Florida, United States

Outcomes

Primary Outcomes

Pharmacokinetic (PK) Parameter : AUClast of Vesatolimod (VES)

AUClast is defined as an area under the concentration versus time curve from time zero to the last quantifiable concentration. Cohort 1 Period 1 Day 1: Day 1 from Baseline; Cohort 1 Period 2 Day 2: Up to Day 17 from Baseline; Cohort 1 Period 3 Day 3: Up to Day 44 from Baseline; Cohort 2 Period 1 Day 1: Day 1 from Baseline; Cohort 2 Period 2 Day 6: Up to Day 21 from Baseline.

Time frame: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, and 96 hours post-dose for Cohort 1 on Period 1 Day 1, Period 2 Day 2, and Period 3 Day 3; and for Cohort 2 on Period 1 Day 1 and Period 2 Day 6

PK Parameter : AUCinf of VES

AUCinf is defined as an area under the concentration versus time curve extrapolated to infinite time, calculated as AUClast + (Clast/Lambda z). Cohort 1 Period 1 Day 1: Day 1 from Baseline; Cohort 1 Period 2 Day 2: Up to Day 17 from Baseline; Cohort 1 Period 3 Day 3: Up to Day 44 from Baseline; Cohort 2 Period 1 Day 1: Day 1 from Baseline; Cohort 2 Period 2 Day 6: Up to Day 21 from Baseline.

PK Parameter : Cmax of VES

Cmax is defined as the maximum observed concentration of drug. Cohort 1 Period 1 Day 1: Day 1 from Baseline; Cohort 1 Period 2 Day 2: Up to Day 17 from Baseline; Cohort 1 Period 3 Day 3: Up to Day 44 from Baseline; Cohort 2 Period 1 Day 1: Day 1 from Baseline; Cohort 2 Period 2 Day 6: Up to Day 21 from Baseline.

PK Parameter : %AUCexp of VES

%AUCexp is defined as the percentage of AUC extrapolated between AUClast and AUCinf, calculated as (\[AUCinf-AUClast\]/AUCinf)\*100. Cohort 1 Period 1 Day 1: Day 1 from Baseline; Cohort 1 Period 2 Day 2: Up to Day 17 from Baseline; Cohort 1 Period 3 Day 3: Up to Day 44 from Baseline; Cohort 2 Period 1 Day 1: Day 1 from Baseline; Cohort 2 Period 2 Day 6: Up to Day 21 from Baseline.

Data from ClinicalTrials.gov

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